Resorbable (alternatively called absorbable, degradable, bioabsorbable, bio-absorbable, bioresorbable, bio-resorbable, biodegradable, bio-degradable, biocorrodible or bio-corrodible) implants have to date been generally prepared from polymers. Unfortunately, the use of polymers in implants has two serious disadvantages. First, plasticizers harmful to the body can be released from the implant. Furthermore, the mechanical properties of the polymers are often unsatisfactory.
Since the beginning of the 20th century it has been known that implants made of magnesium and its alloys are easily absorbable and biocompatible. The absorbability in the body is based on the corrosion of magnesium in saline immersions. Its essential character for the body's functions and the elimination of excess doses via the urinary tract qualify magnesium as a basic implant substance with a high level of physical and chemical biocompatibility.
The average distribution of magnesium in the body mass is 470 mg/kg, the recommended daily dose is 200 to 300 mg/d MgSO4. Magnesium also has an antiarrhythmic effect and lowers blood pressure and sensitivity to pain. The maximum dose for short-term infusion in a human weighing 75 kg is 57.6 mg pure magnesium. Blood plasma contains, for example, 107 mMol/l, and gastric juice contains 160 mval/l of magnesium chloride ions.
The developments in the first Mg period before World War Two (Verbrugge 1933, McBride 1938, Lambotte 1932) did not result in alloys that corrode sufficiently slowly. The developments in the second Mg period during the Cold War (Stroganov, DE-OS 1 953 241) provided alloys with greater corrosion resistance whose cadmium additive was intended to accelerate bone fusion, but whose toxicity substantially limited its use.
Other more recent magnesium alloys contain rare earth metals, preferably in addition to lithium. With these alloys, the absorption of the implant is considerably delayed, but with these materials there is still an appreciable development of hydrogen and gas pockets in the tissue. For many applications, the rate of corrosion of the alloys containing rare earth metals is still too high, since the stability losses associated with absorption occur too early in the healing or tissue formation process.
The use of surface modifications on such resorbable metallic implants has been mentioned in US20050079088, which aims to use surface modification to improve mechanical and corrosion properties.
It is difficult to culture cells onto resorbable metallic material in a physiologically relevant environment because the ions released and/or the change in pH is likely to harm cells. For example, it is known that the alkaline environment produced by corroding magnesium can kill cells.
However, even if the modification were considered successful, the application would still be limited to hard tissues. Application to soft tissues, membranous tissues, organs or organ parts would appear to be unsuitable because of the perceived rigidity of magnesium or other metallic materials, regardless of the resorbability.
Therefore, the use of resorbable metallic materials for the application on soft tissues, membranous tissues or organs especially for the generation or regeneration of such tissues is a largely unexplored field. Such generation or regeneration of tissues with engineering technique may also be called “tissue engineering”.
From experiments of our team, a tough, dense layer of soft tissue is formed on a piece of magnesium implanted subcutaneously into a mouse. According to literature (Witte F, Ulrich H et. al. (2007) J Biomed Mater Res 81A: 748-756), this layer should be cell-infiltrated collagen, produced by “foreign body response” in the form of fibrosis on biomaterials.
The principle of fibrosis induction had actually been used in the 1980s (Mendes D G, Soudry M, et. al. (1988) Clinical Orthopaedics and Related Research 234:291-295) for the regeneration of ligaments, although without much popularity, and the bio-material used was carbon fiber. Carbon fiber is too stiff, and it does not have the required bioactivity. Either of these factors is sufficient to create the unpopularity of such prior art.
Also intravascular fibrosis-inducing agents are used by some investigators to generate biological tissues by fibrosis for the purpose to facilitate cell anchoring.